Scatter factor of hepatocyte growth factor (SF/HGF) is pleiotropic cytokine that has significant angiogenic activity in vitro and in vivo, and may be a good candidate for therapeutic angiogenesis, i.e. administration of growth factors to stimulate neovascularization in areas of atherosclerotic damage. The Phase I project will evaluate the feasibility of angiogenic gene therapy with SF/HGF in an adenoviral vector in rat models of acute myocardial and peripheral ischemia. The specific aims are 1) to characterize and optimize adenoviral vectors containing SF/HGF coding sequences for use in gene transfer experiments; 2) to test whether direct injection of these vectors results in SF/HGF expression, whether this expression is localized, and whether it is specific for ischemic tissue; and 3) to determine if SF/HGF transduction induces angiogenesis in vivo. Successful completion of the Phase I studies will lead to confirmatory experiments in larger animal models of chronic myocardial and peripheral ischemia in Phase II that will be the basis for a IND filing and clinical studies of SF/HGF gene therapy. PROPOSED COMMERCIAL APPLICATIONS: The Phase I and Phase II projects are designed to provide the key pre- clinical data to support regulatory filing and lunch of clinical trials of SF/HGF gene therapy. Angion Biomedica Corp. has signed a technology transfer agreement with North Shore University Hospital that includes an exclusive licence for US Patient 5837676, "Use of Scatter Factor to Enhance Angiogenesis". The company expects to pursue clinical development and commercialization of SF/HGF gene therapy to treat coronary artery disease and peripheral vascular disease in collaboration with a pharmaceutical industry partner. Cardiovascular disease is the leading cause of morbidity and mortality in the US and the largest segment of the health care market.